Clinical Trials Report Central & Peripheral Nervous Systems: Drugs in development for the treatment of multiple sclerosis: antigen non-specific therapies

References

• LUBLIN FL), REINGOLD SC FOR THE NATIONAL MULTIPLE SCLEROSIS SOCIETY: Defining the clinical course ofmultiple sclerosis. Results of an international survey. Neurology (1996) 46:907-911. Terminology of MS types differs from country to country, even clinic to clinic. This paper recommends a standardised classification which should be adopted for future clinical trials.
   Google Scholar
• SWINGLER RJ, COMPSTON DAS: The morbidity of multi - pie sclerosis. Quart. J. Med. (1992) 83: 325–337. A good presentation of morbidity data from the UK.
   Google Scholar
• FFRENCH-CONSTANT C: Pathogenesis of multiple scle- rosis. Lancet (1994) 343: 271–274. A concise discussion of MS pathology.
   Google Scholar
• KHOURY SJ, GLJTTMANN CRG, ORAV EJ et al.: Longitudi-nal MRI in multiple sclerosis: correlation between dis-ability and lesion burden. Neurology (1994) 44:2120–2124.
   PubMed Web of Science ®Google Scholar
• THOMPSON AJ, ICERMODE AG, WICKS D et aL: Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann. Neurol. (1991) 29:53-62. This paper illustrates important differences in disease dynamics between these two groups of patients, underlining the need to carefully define the patient group(s) entered into clinical trials.
   Google Scholar
• THOMPSON AJ, MILLER DH, YOUL BD et al: Serial gad-olinium enhanced MRI in relapsing remitting multiple sclerosis of varying disease duration. Neurology (1992) 42:60–63.
   PubMed Web of Science ®Google Scholar
• COMI G, FILIPPI M, MATINELLI V et al.: Brain MRI corre-lates of cognitive impairment in primary and secondary progressive multiple sclerosis. J. Neurol. Sci. (1995) 132:222–227.
   PubMed Web of Science ®Google Scholar
• RON MA, CALLANAN MM, WARRINGTON EK: Cognitive abnormalities in multiple sclerosis: a psychometric and MB! study. Psychological Medicine (1991) 21:59–68.
   PubMed Web of Science ®Google Scholar
• BARICHOF F, TAS MW, FREQUIN STEM et al.: Limited duration of the effect of methylprednisolone onchanges on MRI in multiple sclerosis. Neuroradiology (1994) 36:382–387.
   PubMed Web of Science ®Google Scholar
• MILLFR DH, THOMPSON HJ, MORRISSEY SECONDARY-PROGRESSIVE MACMANUS DG et al.: High dose steroids In acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect. J. Neurol. Neurosurg. Psychiatry (1992) 55:450-453. References [9] and [10] describe the short-term suppressive effect of corticosteroids on lesion activity.
   Google Scholar
• WEINER HL, MACKIN GA, ORAV Intermittent cyclo-phosphamicle pulse therapy in progressive multiple sclerosis: final report of the Northeast Co-operative Multiple Sclerosis Treatment Group. Neurology (1993) 43:910–918.
   PubMed Web of Science ®Google Scholar
• YUDKIN PL, ELLISON GW, GHEZZI A et al.: Overview of azathioprine treatment in multiple sclerosis. Lancet (1991) 338:1051-1055. Useful summary of clinical trials, concluding that "it is debatable whether the slight clinical effects of azathioprine outweigh its side-effects."
   Google Scholar
• VAN ()OSTEN BW, TRUYEN L, BARKHOF F, POLMAN, CH: Multiple sclerosis therapy: a practical guide. Drugs (1995) 49:200–212.
   Google Scholar
• THE IFNI( MULTIPLE SCLEROSIS STUDY GROUP: Inter-feron beta-lb is effective in relapsing-remitting multi-ple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial Neurology (1993) 43:655–661.
   Google Scholar
• PATY DW, LI DICB, THE UBC MS/MRI STUDY GROUP AND THE IFNf) MULTIPLE SCLEROSIS STUDY GROUP: Inter-feron beta-lb is effective in relapsing-remitting multi-ple sclerosis. II. MIU analysis results of a multicenter, randomized, double-blind, placebo-controlled trial Neurology (1993) 43:662–667.
   Google Scholar
• THE IFNI3 MULTIPLE SCLEROSIS STUDY GROUP et at: Interferon beta-lb in the treatment of multiple sclero-sis: final outcome of the randomized controlled triaL Neurology (1995) 45:1277-1285. References [14-16] present the Betaferon pivotal trial data.
   Google Scholar
• JOHNSON ICP, BROOKS BR, COHEN JA et al. AND THE COPOLYMER 1 MULTIPLE SCLEROSIS STUDY GROUP: Co-polymer-1 reduces relapse rate and improves disability In relapsing-remitting multiple sclerosis: results of a Phase III multicenter, double-blind, placebo-controlled trial. Neurology (1995) 45:1268-1276. Pivotal Copaxone trial data.
   Google Scholar
• COHEN JA, GROSSMAN RA, UDUPA JK et al.: Assessment of the efficacy of Copolymer-1 in the treatment of multiple sclerosis by quantitative MRL Neurology (1995) 45\(Suppl. 4)A418.
   Google Scholar
• BECK RW, TROBE JD FOR THE OPTIC NEURITIS STUDY GROUP: What have we learned from the optic neuritis treatment trial? Opthalmology (1995) 102:1504–1508.
   PubMed Web of Science ®Google Scholar
• SADOVNICK AD, REMICK RA, ALLEN J et aL: Depression and multiple sclerosis. Neurology (1996) 46:628–632.
   PubMed Web of Science ®Google Scholar
• POSER CM, PATY DW, SHEINBERG L et aL: New diagnostic criteria for multiple sclerosis: guidelines for researchprotocols. Ann. Neurol. (1983) 13(3):227–231. Definitive paper outlining the diagnostic criteria for MS.
   Google Scholar
• KURTZKE JF: Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).Neurology (1983) 33:1444-1452. The most widely accepted clinical disability scale for MS. Comparison of post-treatment EDSS scores or progression of disability measured using this scale are the usual primary end-points in Phase III MS
   Google Scholar
• SIPE JC, ICNOBLER RL, BRAHENY SL et al.: A neurologic rating scale (NRS) for use in multiple sclerosis. Neurol-ogy (1984) 34:1368-1372. An alternative scale, usually referred to as the 'Scripps scale' or SNRS.
   Google Scholar
• GOODIUN DE, COOKFAIR D, WENDE K et aL AND THE MULTIPLE SCLEROSIS COLLABORATIVE RESEARCH 15. ��17. �� GROUP: Inter- and intrarater scoring agreement using grades 1.0 to 3.5 of the Kurtzke expanded disability status scale (EDSS). Neurology (1992) 42:859-863. This study illustrates some of the limitations of the EDSS and emphasises the need for training of assessors.
   Google Scholar
• SHARRACK B, HUGHES RAC: Clinical scales for multiple sclerosis. J. Neurol. Set. (1996) 135:1-9. A critical review of many of the various scales and end-points, including EDSS and SRNS, used in MS clinical trials.
   Google Scholar
• MILLER DH, ALBERT PS, BARKHOF F et al: Guidelines for the use of magnetic resonance techniques in monitor-ing the treatment of multiple sclerosis. Ann. Neurol. (1996) 39:6-16. Essential reading for those designing (early phase) MS drug trials in which MRI may be used as the primary end-point.
   Google Scholar
• LANKHORST GJ, JELLES F, SMITS RCF etal.: Quality of lifein multiple sclerosis: the disability and impact profile (DIP). J. Neurol. (1996) 243:469–474.
   Google Scholar
• SPACK EG: Antigen-specific therapies for multiple scle-rosis. Exp. Opin. Invest. Drugs (1996) 5(10):1331–1348.
   Google Scholar
• JACOBS LD, COOKFAIR DL, RUDICK RA et al.: Intramus- cular interferon beta-la for disease progression inrelapsing multiple sclerosis. Ann. Neurol. (1996) 39:285-294. The Avonex pivotal trial data.
   Google Scholar
• F-D-C REPORT: Biogen Avonex FDA Committee findings.The Pink Sheet (11 December, 1995).
   Google Scholar
• POZZILI C, KOUDRIAVTSEVA T, GASPERINI C et al.: Theeffect of r1FNC- 1 a on monthly Gd-enhanced MRI and relapse rate in multiple sclerosis: results of 9-month treatment period. Neurology (1996) 46\(Suppl. 2). Abstract S52.004.
   Google Scholar
• ANON: Phase WM multiple sclerosis trial with Ares-Se-rono's interferon beta-la shows a two-third reduction In exacerbation rate. Press Release (21 June, 1995).
   Google Scholar
• ANON: New Italian 1F-beta trial in MS. Scrip (1 August,1995) 2046:19.
   Google Scholar
• DURELLI L, BONGIOANNI MR, CAVALLO R et al.: Chronicsystemic high-dose recombinant interferon affa-2a re-duces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in re-lapsing-remitting multiple sclerosis. Neurology (1994) 44:406–413.
   PubMed Web of Science ®Google Scholar
• KARUSSIS DM, MEINER Z, LEHMANN D et al.: Treatment of secondary progressive multiple sclerosis with the inummomodulator Linomicle: a double-blind placebo-controlled pilot study with monthly MRI evaluation. Neurology (1996) 47:341–346.
   PubMed Web of Science ®Google Scholar
• ANDERSEN 0, LYCKE J, TOLLESSON PO et al.: Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis. J. NeuroimmunoL (1995) Suppl. 1:26.
   Google Scholar
• KARUSSIS DM, LEHMANN D, OVADIA H et al.: Immu-nological evaluation in patients with secondary pro-gressive multiple sclerosis treated with Linomide. Neurology (1996) 46\(Suppl. 2). Abstract P03.088
   Google Scholar
• BEUTLER E, SIPE JC, ROMINE JS et al: The treatment of chronic progressive multiple sderosis with cladribine. Proc. Natl. Acad. Sci. USA (1996) 93:1716-1720. Data from a 2-year study showing possible benefit of cladribine in treating chronic progressive MS.
   Google Scholar
• BEUTIER E, SIPE JC, ROMINE J et al.: Treatment of multi-ple sclerosis and other autoimmune diseases with cladribine. Semin. Hematol. (1996) 33\(Suppl. 1):43–52.
   Google Scholar
• DECASTRO S, CARTONI D, MILLEFIORINI E etal.: Non-in-vasive assessment of mitoxantrone cardiotoxicity in relapsing remitting multiple sclerosis. J. din. Pharma-col. (1995) 35:627–632.
   Google Scholar
• STECCHI S, SCANDELLARI C, SABA E, MONTARI E: Mitox-antrone therapy in relapsing-progressive (RP) and chronic (chronic progressive) multiple sclerosis. J. Neurol (1996) 243\(No.6, Suppl. 2):283.
   Google Scholar
• MERICELBACH S, HAASS A, HEIDE G, SCHIMRIGK K: Treat-ment of rapid progressive multiple sclerosis (MS) with mitoxantrone. J. Neurol. (1996) 243\(No.6, Suppl. 2):280.
   Google Scholar
• ANON: Novantrone in MS: new trial shows benefit. Pharmaceutical Business News (13 March, 1996).
   Google Scholar
• 'THOMPSON AJ, NOSEWORTHY JH: New treatments for multiple sderosis: a clinical perspective. Curr. Opin. Neurol. (1996) 9:187-198. A good clinical review of current and new MS therapies.
   Google Scholar
• KAPPOS L, RADU EVIT, DELTAS S et al AND THE 15+ DSG STUDY GROUP: 15+ deoxyspergualine (DSG) in the treatment of active MS: final analysis of the European Multicenter Study. Neurology (1996) 46\(Suppl. 2). Abstract S55.001.
   Google Scholar
• ACHIRON A, GABBAY U, GILAD R et al.: Intravenous immunoglobulin (IVIg) in multiple sclerosis: a multi-centre double-blind placebo-controlled trial Neurology (1996) 46\(Suppl. 2). Abstract S52.001.
   Google Scholar
• BARKHOF F, THOMPSON AJ, HODGKINSON S et al.: Dou- ble-blind, placebo-controlled, MRI monitored explora-tory trial of chimeric anti-CD4 antibodies in MS. J. Neuroimmunol. (1995) Suppl. 1:15. Disappointing results for a novel approach to irrununosuppression in MS.
   Google Scholar
• MOREAU T, THORPE J, MILLER D et al.: Preliminary evidence from magnetic resonance imaging for reduc-tion in disease activity after lymphocyte depletion in multiple sclerosis. lancet (1994) 344:298-301. Preliminary data on the CAMPATH-1H antibody.
   Google Scholar
• YEDNOCK TA, CANNON C, FRITZ LC etal.: Prevention of experimental autohnmune encephalomyelitis by anti-bodies to a4131 'Merin. Nature (1992) 356:63–66.
   Google Scholar
• KENT SJ, KARLIK SJ, CANNON C et al.: A monoclonal antibody to 4 integrin suppresses and reverses active experimental allergic encephalomyelitis./ Neuroimmu-nol. (1995) 58:1-10. References [491 and [501 describe activity of an antibody to a4131 integrin in EAE. This antibody, Antegren, has now progressed to clinical trials.
   Google Scholar
• THE MULTIPLE SCLEROSIS STUDY GROUP: Efficacy andtoxicity of cyclosporine in chronic progressive multi-ple sclerosis: a randomised, double-blinded, placebo-controlled clinical triaL Ann. Neurol. (1990) 27:591–605.
   Google Scholar
• GOODKIN DE, RUDICK RA, MEDENDORP SV et al.: Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann. Neurol. (1995) 37:30–40.
   Google Scholar
• OLEK MJ, HOHOL MJ, WEINER HL: Methotrexate in thetreatment of multiple sclerosis. Ann. Neurol. (1996) 39:684.29.
   PubMedGoogle Scholar
• ANON: Scotia licenses MS therapy. Scrip (13 February,1996) 2102.
   Google Scholar
• KRUPP LB, COYLE PK, DOSCHER C et aL: Fatigue therapyIn multiple sclerosis: Results of a double-blind, random-ized, parallel trial of amantidine, pemoline, and pla-cebo. Neurology (1995) 45:1956–1961.
   PubMed Web of Science ®Google Scholar
• POLMAN CH, BERTELSMANN FW, VAN LOENEN AC, KOET-STER JC: 4-Aminopyridine in the treatment of patients with multiple sclerosis. Long term safety and efficacy. Arch. Neurot (1994) 51:292–296.
   PubMed Web of Science ®Google Scholar
• BEVER CT, YOUNG D, ANDERSON PA et at: The effects of4-Aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology (1994) 44:1054–1059.
   PubMed Web of Science ®Google Scholar